Biology subjects

Meyer, E. M. M.

Publications and source records attributed to Meyer, E. M. M..

2 recordsLinked to original sources

bioRxiv2025

Stable fusion of bone marrow-derived cells with Purkinje neurons enables long-term nuclear integration and neuronal repair

Developing effective strategies to replace or restore injured neurons could significantly revolutionise the treatment of currently incurable neurodegenerative disorders. Studies have shown that bone marrow-derived cells (BMDCs) can migrate into the brain and fuse with damaged Purkinje neurons (PNs), restoring their structure and function. Yet, despite over two decades of research, the temporal dynamics and functional stability of these fusion events in vivo remain poorly defined, largely due to reliance on static, post-mortem histological analyses that provide only a single snapshot in time. Here, using in vivo two-photon imaging of the intact cerebellum in EGFP-bone marrow chimeric mice, we visualised the dynamics of BMDC-PN interactions both in real time and longitudinally to monitor the physiological characteristics of fused PNs. Notably, we provide definitive evidence that fused cells are not transient but remain stable over extended periods in the living brain. Moreover, we demonstrate sustained transcriptional activity of donor-derived genes within fused PNs, indicating partial or complete functional integration of the BMDC nucleus. Given their accessibility and genetic tractability, BMDCs represent a practical and promising platform for targeted delivery of therapeutic genes to PNs, opening new avenues for treating neurodegenerative disease.

neuroscience↗

bioRxiv2025

Tactile stimulation transiently disrupts encoding of whisker position by cerebellar molecular layer interneuron ensembles

Molecular layer interneurons (MLIs) within the cerebellar cortex mediate feed-forward inhibition onto Purkinje cells, positioning them as pivotal modulators of cerebellar output. We asked how motor patterns and salient sensory input influence MLI population activity during active whisking and tactile interactions. Utilizing two-photon calcium imaging combined with high-speed videography, we examined MLI population dynamics in awake, behaving mice engaged in voluntary whisker movements. Our results demonstrate that during free whisking, MLI population activity reliably tracks whisker position, yielding uniform graded responses that provide stable and precise representations over time. Tactile contact with external stimuli evokes additional activation in a subset of MLIs. Sensory input transiently disrupts the linear relationship between MLI activity and whisker position and may account for rapid synchronous inhibition of Purkinje cell spiking activity following tactile stimulation. These findings indicate that MLIs in Crus 1 maintain an accurate internal model of whisker position which is perturbed upon encountering obstacles. This disruption likely reflects the integration of sensory feedback, disrupting predictive signals that are subsequently passed forward to Purkinje cells. Such signals can alert the brain to novel happenings and be used to update motor commands, thereby contributing to cerebellar function in response to environmental changes.

neuroscience↗